Targeting neutrophil extracellular traps with a biomimetic patch to inhibit epidural fibrosis

Background: Epidural fibrosis, a major contributor to failed back surgery syndrome, involves post-operative scar adhesion and nerve compression leading to persistent pain and compromised outcomes. While neutrophil extracellular traps (NETs) are implicated in pathological scar formation, effective and sustained strategies to modulate their activity are lacking. This study aimed to leverage the anti-NETs potential of curcumin, overcoming its inherent limitations of poor bioavailability, for the active prevention of epidural fibrosis. Methods: Curcumin (Cur) was encapsulated within core–shell poly (L-lactic acid) micro-sol electrospun fibers (MS@Cur) to enable localized, sustained delivery. The release profile and physicochemical properties of the fabricated membranes were characterized. In vitro studies evaluated their cytocompatibility and their ability to inhibit NETs formation by neutrophils. Efficacy was further evaluated in a rat laminectomy model, where the impact of MS@Cur implantation on NETs markers (myeloperoxidase and citrullinated histone H3), collagen deposition, and myofibroblast activation was analyzed histologically. Results: The MS@Cur membranes demonstrated successful curcumin encapsulation, mitigating burst release and achieving sustained release for over 28 days. They showed favorable cytocompatibility and effectively inhibited NETs formation in vitro . In vivo , implantation of MS@Cur led to a notable downregulation of NETs markers. Histological analyses confirmed a significant reduction in excessive collagen deposition and aberrant myofibroblast activation at the laminectomy site. Conclusion: The developed biomimetic dural patch enables sustained and efficient local delivery of curcumin, effectively modulating NETs formation after laminectomy. This strategy represents a novel and effective therapeutic approach for the active prevention of epidural scar formation following dural injury, with significant translational potential.